1. Technical Field
The invention relates to methods and materials involved in the treatment and prevention of non-invasive fungus-induced inflammation of mucosal tissue as well as asthma symptoms.
2. Background Information
Mucositis, the inflammation of mucosal tissue, is a serious medical problem that affects millions of people worldwide. For example, conservative estimates indicate that between 20 to 40 million Americans suffer from chronic rhinosinusitis, an inflammation of the nasal cavity and/or paranasal sinuses.
For the most part, the cause of chronic rhinosinusitis is unknown. In a small percentage of patients, however, non-invasive fungal organisms living within mucus seem to be involved. Patients having this condition, now known as allergic fungal sinusitis (AFS), were first described in the early 1980""s (Miller J W et al., Prod. Scot. Thor. Soc. 36:710 (1981) and Katzenstein A L A et al., J. Allergy Clin. Immunol. 72:89-93 (1983)). Specifically, about three to eight percent of chronic rhinosinusitis cases requiring surgery because of nasal obstruction caused by polyp formation have been classified as AFS. Briefly, AFS is diagnosed by the presence of inspissated mucus in the nasal-paranasal cavities. Typically, this mucus contains clumps or sheets of necrotic eosinophils, Charcot-Leyden crystals, and non-invasive fungal hyphae. In addition, patients with AFS typically have a history of nasal-paranasal polyposis and may have undergone multiple surgeries. Inflammation can affect all nasal-paranasal cavities, but also can be asymmetric involving only one side. Computed topography (CT) scans of patients with AFS have a characteristic appearance and often reveal bone erosion in adjacent structures. Indeed, destruction of bones adjacent to the sinuses and nasal areas ranging from 19 percent to 80 percent has been reported.
Although fungal organisms seem to be the causative agent of AFS, successful treatment remains lacking. Currently, AFS patients as well as most chronic rhinosinusitis patients receive surgical treatment with or without steroid therapy. Surgery helps clear the nasal-paranasal cavities when obstructed by polyps and steroid therapy helps control inflammatory responses that seem to be causing tissue and bone destruction. Unfortunately, patients treated with surgery alone almost always experience recurrent rhinosinusitis symptoms and additional polyp growth. In addition, prolonged use of steroids is associated with significant side effects and steroid therapy removal also leads to recurrent episodes of rhinosinusitis. For these reasons, people suffering from chronic rhinosinusitis conditions typically experience repeated cycles of intense inflammation, surgery, and steroid therapy followed by recurrent intense inflammation. Thus, neither surgery nor steroid therapy is particularly effective or desirable as a long-term treatment for chronic rhinosinusitis conditions.
The present invention relates generally to methods and materials for treating and preventing non-invasive fungus-induced mucositis. The term xe2x80x9cmucositisxe2x80x9d as used herein means an inflammation, as opposed to an infection, of a mucus membrane. This invention is based on the discovery that the condition known as AFS can be treated successfully by using an antifungal agent in an amount, at a frequency, and for a duration effective to reduce inflammation caused by the presence of fungal organisms within nasal-paranasal mucus. In addition, this invention is based on the discovery that using an antifungal agent in an amount, at a frequency, and for a duration effective to maintain a reduced level of fungal organisms within nasal-paranasal mucus can prevent AFS symptoms. Specifically, the invention involves administering an antifungal agent to a mammal such that the antifungal agent contacts the mammal""s mucus and reduces the presence of fungal organisms in mucus. In addition to being the only known method for successfully treating and preventing AFS, the use of an antifungal agent is particularly advantageous to a patient when compared to other currently available medical approaches to AFS such as surgical treatments and steroid therapies. Such medical approaches can have side effects, can be costly, and may be associated with patient discomfort.
This invention is also based on the discovery that most, if not all, chronic rhinosinusitis conditions have a fungal etiology and that most, if not all, cases of chronic rhinosinusitis can be treated by using an antifungal agent in an amount, at a frequency, and for a duration effective to reduce the presence of fungal organisms within nasal-paranasal mucus. In addition, using an antifungal agent in an amount, at a frequency, and for a duration effective to maintain a reduced level of fungal organisms within nasal-paranasal mucus can prevent chronic rhinosinusitis symptoms.
This discovery is contrary to the current understanding of chronic rhinosinusitis and has far-reaching implications within medicine. For example, numerous medical research articles report that about three to eight percent of chronic rhinosinusitis cases requiring surgery are AFS, a rhinosinusitis condition having a non-invasive fungal etiology. In fact, less than 150 cases of AFS have been reported in the literature over the past 15 years. It is noted that the lack of appreciation for the non-invasive fungal etiology of chronic rhinosinusitis conditions may have occurred since affected individuals are frequently found to have bacterial infections (i.e., invasive bacteria). Presumably, tissue damage caused by non-invasive fungus-induced inflammation results in a higher occurrence of bacterial infections in those damaged areas. Thus, overlaying bacterial infections in affected individuals could have masked the underlaying cause, fungal organisms within mucus.
For the purpose of this invention, the term xe2x80x9cnon-invasive fungus-induced rhinosinusitisxe2x80x9d includes AFS as well as any other nasal-paranasal mucositis condition having a non-invasive fungal etiology.
Treating and preventing non-invasive fungus-induced rhinosinusitis, whether diagnosed as AFS or any other rhinosinusitis condition having a non-invasive fungal etiology, by using an antifungal agent circumvents the need for surgical treatments and steroid therapies that cause significant pain and suffering to the patient. Moreover, the use of antifungal agents to treat and prevent non-invasive fungus-induced rhinosinusitis actually directs treatment against the etiological agent (i.e., fungus), unlike surgical treatments, steroid therapies, and antibacterial treatments.
The term xe2x80x9cchronicxe2x80x9d as used herein refers to afflictions present for at least three months. It is to be understood that afflictions that are treated as described herein and become asymptomatic can be classified as chronic. Thus, chronic afflictions can be symptomatic or asymptomatic.
This invention is also based on another, equally significant, discovery that chronic asthma symptoms can be treated and prevented successfully by using an antifungal agent in an amount, at a frequency, and for a duration effective to reduce the presence of fungal organisms within airway mucus. It is also apparent from the present discoveries that antifungal agents can be administered directly to the lung airways for the treatment of chronic asthma. Again, these discoveries are contrary to the current understanding of chronic asthma and have far-reaching clinical implications. Taken together, these significant breakthroughs can potentially allow large populations to experience happier, healthier, and more productive daily lives.
Specifically, the invention provides methods and materials for treating and preventing a wide variety of mucoinflammatory diseases by using an antifungal agent. The use of an antifungal agent is a safe and highly effective treatment approach that involves mucoadministering an antifungal agent in an amount, at a frequency, and for a duration effective to reduce, prevent, or eliminate a non-invasive fungus-induced mucositis. The term xe2x80x9cmucoadministrationxe2x80x9d as used herein refers to any type of administration that places an administered agent in contact with mucus. This invention also provides specific antifungal formulations that can be applied to the various parts of a mammal that contain mucus. In addition, the invention provides medical devices that can be used to apply antifungal formulations. These devices are particularly advantageous since they can be used by an individual to administer an effective dose of a specific antifungal formulation to the appropriate area of the body. Further, the invention provides improved methods and materials for collecting and culturing fungal organisms from mucus samples. These culturing techniques can be used to monitor the number of fungal species within mucus during a particular antifungal treatment regimen. In addition, these fungus collecting and culturing methods and materials are useful for identifying the genotype and phenotype of specific fungal organisms that cause non-invasive fungus-induced mucositis. The identification and characterization of non-invasive fungal organisms found in a particular individual""s mucus can assist clinicians in determining proper treatment and prophylactic approaches. For example, this information can help determine the specific antifungal agent, amount, mode of administration, and number of applications to be used as well as possible combinatorial therapies that may include other medications and procedures such as steroids, antibacterial agents, and surgery.
In general, the invention features a method for treating a mammal (e.g., human) having non-invasive fungus-induced rhinosinusitis. This method involves directly mucoadministering to at least a portion of the mammal""s nasal-paranasal anatomy a formulation in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced rhinosinusitis. This formulation contains an antifungal agent or a plurality of antifungal agents and can be in a solid, liquid, or aerosol form (e.g., a powder, crystalline substance, gel, paste, ointment, salve, cream, solution, suspension, partial liquid, spray, nebulae, mist, atomized vapor, aerosol, and tincture). In addition, the formulation can be in a form suitable for self-mucoadministration by a human.
Further, the formulation can contain a pharmaceutically acceptable aqueous vehicle (e.g., saline and water). For example, a liquid form of the formulation can contain about 0.00001 percent to about 20 percent of an antifungal agent as determined by antifungal agent weight per aqueous vehicle volume. In addition, the formulation can contain about 0.01 ng to about 1000 mg of an antifungal agent (e.g., amphotericin B) per liter in some embodiments of the invention, or about 1 ng to about 500 mg of an antifungal agent per liter in other embodiments of the invention, or about 100 mg of an antifungal agent per liter in still other embodiments of the invention. In addition, an effective amount of these aqueous formulations can be about 0.01 mL to about 1 L of formulation per nostril in some embodiments of the invention, or about 5 mL to about 100 mL of formulation per nostril in other embodiments of the invention, or about 40 mL of formulation per nostril in still other embodiments of the invention. Alternatively, an effective amount of a formulation can be about 0.01 ng to about 1000 mg of an antifungal agent per kg of body weight of the mammal in some embodiments of the invention or about 1 ng to about 500 mg of an antifungal agent per kg of body weight of the mammal in other embodiments of the invention. The effective amount of a formulation can change or remain the same during an effective duration. The effective frequency of direct mucoadministration can be from about four times a day to about once every other week in some embodiments of the invention, or from about twice a day to about once a week in other embodiments of the invention, or about twice a day in still other embodiments of the invention. In addition, the effective frequency of direct mucoadministration can be greater than once a day, or greater than once a week. The effective duration can be greater than about 7, 14, 30, 60, or 90 days.
The mammal can be atopic or nonatopic and can be immunocompetent or immunocompromised. In addition, the non-invasive fungus-induced rhinosinusitis can be characterized by polyp formation or polypoid change. The non-invasive fungus-induced rhinosinusitis also can be a chronic condition. Mucoadministration can be an irrigation of at least a portion of the nasal-paranasal anatomy with a liquid form of the formulation. Alternatively, the mucoadministration can involve applying an aerosol form of the formulation to at least a portion of the nasal-paranasal anatomy. An antifungal agent can be in a solid, liquid, or aerosol form. In addition, an antifungal agent can be a polyene macrolide, tetraene macrolide, pentaenic macrolide, fluorinated pyrimidine, imidazole, azole, triazole, halogenated phenolic ether, thiocarbamate, allylamine, sterol inhibitor, and an agent that interpolates fungal cell wall components. Such antifungal agents include amphotericin B, flucytosine, ketoconazole, miconazole, itraconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, saperconazole, voriconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield""s ointment, propionic acid, and caprylic acid. In addition to containing an antifungal agent, the formulation can contain, without limitation, a pharmaceutically acceptable aqueous vehicle, pharmaceutically acceptable solid vehicle, steroid, mucolytic agent, antibacterial agent, anti-inflammatory agent, immunosuppressant, dilator, vaso-constrictor, decongestant, leukotriene inhibitor, anti-cholinergic, anti-histamine, therapeutic compound, and combinations thereof.
The method can also involve administering a second formulation that contains, without limitation, an antifungal agent, antibacterial agent, steroid, mucolytic agent, anti-inflammatory agent, immunosuppressant, dilator, vaso-constrictor, decongestant, leukotriene inhibitor, anti-cholinergic, anti-histamine, therapeutic compound, or combination thereof. Likewise, the method can involve an additional step after the direct mucoadministration. This additional step can be a prophylactic mucoadministration of a prophylactic formulation to the mammal in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced rhinosinusitis. This prophylactic formulation also contains an antifungal agent and can be in a solid, liquid, or aerosol form (e.g., powder, crystalline substance, gel, paste, ointment, salve, cream, solution, suspension, partial liquid, spray, nebulae, mist, atomized vapor, aerosol, tincture, pill, capsule, tablet, and gelcap). In addition, the prophylactic mucoadministration can be a direct or indirect mucoadministration. For example, the prophylactic mucoadministration can be an irrigation of at least a portion of the nasal-paranasal anatomy with a liquid form of the prophylactic formulation, an application of an aerosol form of the prophylactic formulation to at least a portion of the nasal-paranasal anatomy, or an oral administration of the prophylactic formulation to the mammal in the form of a solid or liquid.
It will be understood that each of the additional features of the invention described above can be applied to the following additional embodiments and aspects of the invention. For example, methods for prophylactically treating a mammal at risk for developing non-invasive fungus-induced rhinosinusitis, and methods for treating asthma, may utilize a formulation in which the antifungal agent is about 0.00001 percent to about 20 percent by weight or volume of a formulation, and so forth.
In another embodiment, the invention features a method for prophylactically treating a mammal at risk for developing non-invasive fungus-induced rhinosinusitis. This method involves mucoadministering to the mammal a formulation in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced rhinosinusitis. This formulation contains an antifungal agent.
Another embodiment of the invention features a method for treating a mammal having non-invasive fungus-induced rhinosinusitis. This method involves the steps of identifying (e.g., diagnosing) the mammal, and directly mucoadministering a formulation to at least a portion of the nasal-paranasal anatomy of the mammal in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced rhinosinusitis. This formulation contains an antifungal agent.
Another embodiment of the invention features a method for prophylactically treating a mammal at risk for developing non-invasive fungus-induced rhinosinusitis. This method involves the steps of identifying the mammal (e.g., diagnosing), and mucoadministering a formulation to at least a portion of the nasal-paranasal anatomy of the mammal in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced rhinosinusitis. This formulation contains an antifungal agent.
In another aspect, the invention features a method for treating a mammal having asthma. This method involves directly mucoadministering to at least a portion of the airways (e.g., nasal-paranasal airways and lung airways) of the mammal a formulation in an amount, at a frequency, and for a duration effective to reduce or eliminate asthma symptoms. This formulation contains an antifungal agent. The direct mucoadministration can be the irrigation of the nasal-paranasal anatomy of the mammal with a liquid form of the formulation. Alternatively, the direct mucoadministration can be the inhalation of the formulation through the mammal""s mouth or nose. In addition, the method can involve an additional step after the direct mucoadministration. This additional step can be the prophylactic mucoadministration of a prophylactic formulation to the mammal in an amount, at a frequency, and for a duration effective to prevent asthma symptoms. This prophylactic formulation also contains an antifungal agent.
In another embodiment, the invention features a method for prophylactically treating a mammal at risk for developing asthma. This method involves mucoadministering to at least a portion of the airways (e.g., nasal-paranasal airways and lung airways) of the mammal a formulation in an amount, at a frequency, and for a duration effective to prevent asthma symptoms. This formulation contains an antifungal agent.
Another embodiment of the invention features a method for treating a mammal having asthma. This method involves the steps of identifying (e.g., diagnosing) the mammal, and directly mucoadministering a formulation to at least a portion of the airways (e.g., nasal-paranasal airways and lung airways) of the mammal in an amount, at a frequency, and for a duration effective to reduce or eliminate asthma symptoms. This formulation contains an antifungal agent.
Another embodiment of the invention features a method for prophylactically treating a mammal at risk for developing asthma. This method involves the steps of identifying the mammal (e.g., diagnosing), and mucoadministering a formulation to at least a portion of the airways (e.g., nasal-paranasal airways and lung airways) of the mammal in an amount, at a frequency, and for a duration effective to prevent asthma symptoms. This formulation contains an antifungal agent.
In another aspect, the invention features a method for treating a mammal having non-invasive fungus-induced intestinal mucositis (e.g., chronic colitis and Crohn""s disease). This method involves mucoadministering to the mammal a formulation in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced intestinal mucositis symptoms. This formulation contains an antifungal agent and can be in the form of a regulated release capsule (e.g., pH or time regulated release capsule). The mucoadministration can be the oral application of the formulation within the digestive tract of the mammal. Alternatively, the mucoadministration can be the application of the formulation within the digestive tract of the mammal by way of an enema.
In another embodiment, the invention features a method for prophylactically treating a mammal at risk for developing non-invasive fungus-induced intestinal mucositis (e.g., chronic colitis and Crohn""s disease). This method involves mucoadministering to the mammal a formulation in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced intestinal mucositis symptoms. This formulation contains an antifungal agent.
In another aspect, the invention features a method for treating a mammal having non-invasive fungus-induced otitis media. This method involves mucoadministering to the mammal a formulation in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced otitis media. This formulation contains an antifungal agent. The mucoadministration can be the application of the formulation within the middle ear of the mammal. For example, a liquid form of the formulation can be used to irrigate the middle ear if the tympanic membrane is elevated or not intact. Alternatively, a formulation can be injected into the middle ear or a myringotomy can be used to penetrate the tympanic membrane. In addition, myringotomy tubes can be used to bypass the tympanic membrane. Further, a formulation can be mucoadministered to the middle ear through the nose and eustachian tube.
In another embodiment, the invention features a method for prophylactically treating a mammal at risk for developing non-invasive fungus-induced otitis media. This method involves mucoadministering to the mammal a formulation in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced otitis media. This formulation contains an antifungal agent.
In another aspect, the invention features an article of manufacture that contains packaging material (e.g., boxes, wrappings, vials, and other containers) and a formulation contained within the packaging material. This formulation contains an antifungal agent. The packaging material contains a label or package insert indicating that the formulation can be directly mucoadministered to at least a portion of the nasal-paranasal anatomy of a mammal having non-invasive fungus-induced rhinosinusitis in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced rhinosinusitis.
In another embodiment, the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent and the packaging material contains a label or package insert indicating that the formulation can be mucoadministered to at least a portion of the nasal-paranasal anatomy of a mammal at risk for developing non-invasive fungus-induced rhinosinusitis in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced rhinosinusitis.
Another embodiment of the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent. The packaging material contains a label or package insert indicating that the formulation can be directly mucoadministered to at least a portion of the airways of a mammal having asthma in an amount, at a frequency, and for a duration effective to reduce or eliminate asthma symptoms.
Another embodiment of the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent and the packaging material contains a label or package insert indicating that the formulation can be mucoadministered to at least a portion of the airways of a mammal at risk for developing asthma in an amount, at a frequency, and for a duration effective to prevent asthma symptoms.
Another embodiment of the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent. The packaging material contains a label or package insert indicating that the formulation can be mucoadministered to a mammal having non-invasive fungus-induced intestinal mucositis in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced intestinal mucositis symptoms.
Another embodiment of the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent and the packaging material contains a label or package insert indicating that the formulation can be mucoadministered to a mammal at risk for developing non-invasive fungus-induced intestinal mucositis in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced intestinal mucositis symptoms.
Another embodiment of the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent. The packaging material contains a label or package insert indicating that the formulation can be mucoadministered to a mammal having non-invasive fungus-induced otitis media in an amount, at a frequency, and for a duration effective to reduce or eliminate non-invasive fungus-induced otitis media symptoms.
Another embodiment of the invention features an article of manufacture that contains packaging material and a formulation contained within the packaging material. This formulation contains an antifungal agent and the packaging material contains a label or package insert indicating that the formulation can be mucoadministered to a mammal at risk for developing non-invasive fungus-induced otitis media in an amount, at a frequency, and for a duration effective to prevent non-invasive fungus-induced otitis media symptoms.
In another aspect, the invention features the use of an antifungal agent for the manufacture of a medicament for the treatment or prevention of non-invasive fungus-induced rhinosinusitis.
In another embodiment, the invention features the use of an antifungal agent for the manufacture of a medicament for the treatment or prevention of asthma symptoms.
Another embodiment of the invention features the use of an antifungal agent for the manufacture of a medicament for the treatment or prevention of non-invasive fungus-induced intestinal mucositis.
Another embodiment of the invention features the use of an antifungal agent for the manufacture of a medicament for the treatment or prevention of non-invasive fungus-induced otitis media.
In another aspect, the invention features an antifungal formulation containing an antifungal agent, a flavoring, and water. The water constitutes at least about 50 percent of the formulation. For example, the water can constitute at least about 55, 60, 65, 70, 75, 80, 85, 90, 95, or 99 percent of the formulation.
In another embodiment, the invention features an antifungal formulation containing itraconazole and water. The itraconazole is dissolved in the formulation at a concentration greater than about 25 xcexcg per mL. For example, the itraconazole can be dissolved in the formulation at a concentration greater than about 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, or 180 xcexcg per mL. In addition, the water constitutes at least about 50 percent of the formulation. For example, the water can constitute at least about 55, 60, 65, 70, 75, 80, 85, 90, 95, or 99 percent of the formulation. The formulation also can contain polyethylene glycol (e.g., PEG-200, PEG-400, PEG-800, etc.). The formulation also can contain flavoring (e.g., peppermint oil, cherry flavoring, syrup, and the like).
In another embodiment, the invention features an antifungal formulation containing itraconazole and water. The itraconazole is suspended in the formulation at a concentration greater than about 25 xcexcg per mL. For example, the itraconazole can be suspended in the formulation at a concentration greater than about 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, or 180 xcexcg per mL. In addition, the water constitutes at least about 50 percent of the formulation. For example, the water can constitute at least about 55, 60, 65, 70, 75, 80, 85, 90, 95, or 99 percent of the formulation. The formulation also can contain polyethylene glycol (e.g., PEG-200, PEG-400, PEG-800, etc.). The formulation also can contain flavoring (e.g., peppermint oil, cherry flavoring, syrup, and the like).
In another embodiment, the invention features an antifungal formulation containing an antifungal agent, a flavoring, and water. The water constitutes at least about 50 percent of the formulation. For example, the water can constitute at least about 55, 60, 65, 70, 75, 80, 85, 90, 95, or 99 percent of the formulation. In addition, the antifungal agent can be amphotericin B, ketoconazole, saperconazole, voriconazole, flucytosine, miconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield""s ointment, propionic acid, and caprylic acid.
In another aspect, the invention features a method of making an antifungal formulation. The formulation contains itraconazole and water. The itraconazole is dissolved in the formulation at a concentration greater than about 25 xcexcg per mL. For example, the itraconazole can be dissolved in the formulation at a concentration greater than about 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, or 180 xcexcg per mL. The water constitutes at least about 50 percent of the formulation. For example, the water can constitute at least about 55, 60, 65, 70, 75, 80, 85, 90, 95, or 99 percent of the formulation. The method includes adding the water to a stock solution containing the itraconazole.
In another aspect, the invention features a method for culturing fungus from a mammal""s mucus. The method includes (1) contacting the mucus with a mucolytic agent to reduce the viscosity of the mucus, (2) separating the fungus from the reduced-viscosity mucus, (3) contacting the separated fungus with fungus growth medium to form a fungus culture, and (4) incubating the fungus culture such that the separated fungus grows.
In another aspect, the invention features a method for obtaining a fungal antigen. The method includes (1) contacting a mammal""s mucus with a mucolytic agent to reduce the viscosity of the mucus, (2) separating fungus from the reduced-viscosity mucus, (3) contacting the separated fungus with fungus growth medium to form a fungus culture, (4) incubating the fungus culture such that the separated fungus grows, and (5) isolating the antigen from the cultured fungus.
In another aspect, the invention features a method for producing a fungus-specific antibody. The method includes (1) contacting a mammal""s mucus with a mucolytic agent to reduce the viscosity of the mucus, (2) separating fungus from the reduced-viscosity mucus, (3) contacting the separated fungus with fungus growth medium to form a fungus culture, (4) incubating the fungus culture such that the separated fungus grows, (5) isolating a fungal antigen from the cultured fungus, and (6) immunizing an animal with the fungal antigen to produce the antibody.
In another aspect, the invention features a nasal mucus collecting apparatus. The apparatus contains a collection retainer, a collection tube, and a connecting portion. The collection retainer is suitable for retaining mucus. The collection tube extends from the collection retainer and defines a distal end and a lumen such that mucus can traverse the lumen from the distal end of the collection tube to the collection retainer. The collection tube is generally flexible over at least a portion of the tube""s length such that the collection tube can be selectively manipulated into a desired configuration by a practitioner during a collection procedure. The collection tube further is generally malleable such that the collection tube generally retains the desired configuration until the practitioner manipulates the collection tube to conform to a different configuration. The connecting portion extends from the collection retainer and defines a second lumen that communicates with the interior of the collection retainer. The connecting portion is adapted to receive a vacuum source. In addition, the apparatus can further contain a valve that adjusts the opening of the second lumen. The collection retainer can be removable from the collection tube and the connection portion.
In another aspect, the invention features a pharmaceutical composition containing an antifungal agent.
In another embodiment, the invention features a pharmaceutical composition containing an antifungal agent and an mucolytic agent.
Another embodiment features a pharmaceutical composition containing an antifungal agent and a steroid.
Another embodiment features a pharmaceutical composition containing an antifungal agent and a decongestant.
Another embodiment features a pharmaceutical composition containing an antifungal agent and an antibiotic.
Another embodiment features a pharmaceutical composition containing an antifungal agent and an anti-inflammatory.
Another embodiment features a pharmaceutical composition containing an antifungal agent and an anti-histamine.
Another embodiment features a pharmaceutical composition containing an antifungal agent and an anti-cholinergic.
Another embodiment features a pharmaceutical composition containing an antifungal agent and a leukotriene inhibitor.
In another aspect, the invention features a composition for treating an immune response to fungus in a mammal, characterized by an agent configured for direct mucoadministration to the mucus of the mammal and having antifungal means for eliminating or reducing the fungus below a threshold level wherein the fungus ceases to activate eosinophile migration to the affected area.
In another aspect, the invention features a pharmaceutical composition for treating a fungal related condition in the nasal-sinus anatomy, pulmonary anatomy, ear anatomy, or intestinal anatomy of a mammalian patient, said composition comprising an effective dose of an anti-fungal as described herein.
In another aspect, the invention features a pharmaceutical composition for treating a fungal related condition in the nasal-sinus anatomy, pulmonary anatomy, ear anatomy, or intestinal anatomy of a mammalian patient, said composition comprising an effective dose of an anti-fungal and at least one other agent or inhibitor as described herein.
In another aspect, the invention features a pharmaceutical composition for treating a fungal related condition in the nasal sinus anatomy, pulmonary anatomy, ear anatomy, or intestinal anatomy of a mammalian patient, said composition comprising an effective dose of an anti-fungal suitable for long term use within the nasal-sinus anatomy.
In another aspect, the invention features a medication for treating sinusitis, asthma, otitis media, or colitis of a patient, comprising a mucolytic agent; and an anti-fungal compound as described herein.
In another aspect, the invention features an irrigation medication for treating an inflamed nasal area, lung area, ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area, or intestinal area being caused by the presence of a fungus, the medication comprising effective doses of an antifungal compound and a steroid as described herein.
In another aspect, the invention features an irrigation medication for treating an inflamed nasal area, lung area, ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area, or intestinal area being caused by the presence of a fungus, the medication comprising effective doses of an antifungal compound and a mucolytic agent.
In another aspect, the invention features an irrigation medication for treating an inflamed nasal area, lung area, ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area, or intestinal area being caused by the presence of a fungus, the medication comprising effective doses of a steroid and a mucolytic agent as described herein.
In another aspect, the invention features an irrigation medication for treating an inflamed nasal area, lung area, ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area, or intestinal area being caused by the presence of a fungus, the medication comprising effective doses of an antifungal compound, a steroid, and a mucolytic agent as described herein.
In another aspect, the invention features an irrigation medication for treating an inflamed nasal area, lung area, ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area, or intestinal area being caused by the presence of a fungus, the medication comprising an effective dose of at least one medicine selected from the group consisting of an antifungal compound, a steroid, a mucolytic agent, and any combination thereof as described herein.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.